Anlotinib followed by transarterial chemoembolization and radiofrequency ablation is a safe and effective initial treatment for hepatocellular carcinoma patients with portal vein tumor thrombus: A retrospective case series study.

BACKGROUND: Portal vein tumor thrombus (PVTT) remains a poor prognostic factor occurring in about 10%-40% of patients with hepatocellular carcinoma (HCC) for the optimal treatment is controversial. Anlotinib is an novel small molecule inhibitor that has a broad spectrum of inhibitory activities on tumor angiogenesis and growth. However, so far, no studies have reported the use of anlotinib in the treatment of HCC patients with PVTT. Here, we evaluated the safety and efficacy of anlotinib, followed by transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for the treatment of patients with HCC and PVTT. MATERIALS AND METHODS: A total of 145 consecutive HCC patients who underwent TACE in combination with RFA were enrolled in the retrospective study. Twenty-eight patients were diagnosed with PVTT and received anlotinib as basic treatment. The adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs Version 4.0. Time to tumor progression (TTP) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: The most common toxicities related to anlotinib were pharyngalgia (53.6%), fatigue (42.9%), and hand-foot skin reaction (39.3%). The median OS was 13 months (range: 3-18 months) with 1-year OS rate of 64.3%. The median TTP was 7 months (range: 1-12 months) with 6-month rate of 46.4%. CONCLUSION: Anlotinib followed by TACE and RFA is a safe and effective initial treatment modality for HCC patients with PVTT. Anlotinib may be a promising therapeutic option for relieving and/or stabilizing HCC with PVTT.

Prognosis in triple-negative apocrine carcinomas of the breast: A population-based study.

BACKGROUND: Triple-negative apocrine carcinoma (TNAC) of the breast is a very rare type of breast cancer. Furthermore, the clinicopathological features, prognosis, and potential impact of treatment strategies in TNAC remain unclear. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program were used to identify breast cancer patients diagnosed between 2010 and 2016 with TNAC and triple-negative breast cancer (TNBC, IDC [invasive ductal carcinoma], NOS [not otherwise specified]). Chi-squared tests were used to examine the categorical variables between the two groups. Overall survival (OS) of TNAC and TNBC was assessed by Kaplan-Meier analyses and Cox regression. Breast cancer-specific survival (BCSS) was evaluated by Nelson-Aalen analyses and competing risk regression. RESULTS: We identified 31 362 patients from the SEER database, including 366 patients with TNAC and 30 996 patients with TNBC. TNAC was correlated with older age, lower T stage and lower tumor grade. Patients with TNAC had better OS compared with TNBC patients; the 5-year OS rates were 82.2% vs 73.5% (P < .001). The breast cancer-related death rate was significantly lower in patients with TNAC than in patients with TNBC, with a 5-year cumulative incidence of 9.1% vs 22.9% (P < .001). Chemotherapy was significantly associated with improved OS in TNAC patients, but radiotherapy was not associated with OS in TNAC patients. In the multivariable Cox regression, TNAC was still associated with improved OS (HR [hazard ratio], 0.61; 95% CI [confidence interval] 0.45-0.83; P = .002). In the multivariable competing risk regression, the significantly higher BCSS in patients with TNAC compared patients with TNBC remained (subdistribution HR [SHR], 0.42; 95% CI, 0.27-0.64; P < .001). CONCLUSION: Patients with TNAC had a better prognosis than patients with TNBC, and chemotherapy was associated with survival advantages in TNAC patients.

Comparison between New-Onset and Old-Diagnosed Type 2 Diabetes with Ketosis in Rural Regions of China.

Objectives. Type 2 diabetes (T2D) with ketosis was common because of late diagnosis and lacking adequate treatment in rural regions of China. This study aimed to provide the data of T2D with ketosis among inpatients in a south-west border city of China. Methods. Data of 371 patients of T2D with ketosis who were hospitalized between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan, China, were analyzed. New-onset and old-diagnosed T2D patients presenting with ketosis were compared according to clinical characteristics, laboratory results, and chronic diabetic complications. Results. Overall, the blood glucose control was poor in our study subjects. Male predominated in both groups (male prevalence was 68% in new-onset and 64% in old-diagnosed groups). Overweight and obesity accounted for 50% in new-onset and 46% in old-diagnosed cases. Inducements of ketosis were 13.8% in new-onset and 38.7% in old-diagnosed patients. Infections were the first inducements in both groups. The prevalence of chronic complications of diabetes was common in both groups. Conclusions. More medical supports were needed for the early detection and adequate treatment of diabetes in rural areas of China.

Characteristics of Type 2 Diabetes with Ketosis in Baoshan, Yunnan of China.

OBJECTIVES: The study provided data to demonstrate the characteristics of type 2 diabetes (T2D) with ketosis in rural parts of south-west border of China in order to help health professionals with optimizing diabetic care. METHODS: All hospitalized adult diabetic patients consecutively between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan province of China, were evaluated. T2D with ketosis, ordinary T2D (without ketosis), and type 1 diabetes (T1D) patients were analyzed according to the clinical and biochemical parameters and chronic complications in these subjects. RESULTS: The prevalence of T2D with ketosis was 12% in the whole study subjects. Overweight and obese patients were predominant (49.1%) in T2D patients with ketosis. The mean HbA1c (13.3 ± 3.1%, P = 0.01), fasting plasma glucose (16.9 ± 6 mmol/L, P < 0.0001), and plasma triglyceride (4.0 ± 4.0 mmol/L, P < 0.0001) in T2D patients with ketosis were significantly higher than ordinary T2D patients without ketosis. Infections were the most common inducements in T2D patients with ketosis. Chronic complications including peripheral neuropathy (34.9%), retinopathy (12.7%), diabetic foot (18.1%), and persistent microalbuminuria (11.7%) were common in T2D patients with ketosis. CONCLUSIONS: . This study indicated the poor glycemic control in diabetic patients in rural areas of south-west part of China. More efforts were urgently required to popularize public health education and improve medical quality in diabetic treatment in these regions.

[Effect of RNA interference targeting-survivin on the invasiveness of human glioma cells in vitro].

OBJECTIVE: To study the role of survivin gene in the invasive behavior of glioma cells and explore the possible mechanism. METHODS: The mRNA and protein expressions of survivin in glioma cell line SNB19 transfected by small interfering RNA (siRNA) targeting survivin were determined by real time RT-PCR and Western blotting, respectively. The anchorage-independent growth of the cells was examined by clone formation assay in soft agar, and their invasiveness was evaluated using a Boyden chamber model. The protein level of urokinase-type plasminogen activator (uPA) was also determined by western blotting. RESULTS: Survivin siRNA dose-dependently inhibited the anchorage-independent growth and invasiveness and reduced the expression of uPA protein in SNB19 cells. CONCLUSION: RNA interference targeting survivin can inhibit the invasiveness of glioma cells in vitro possibly by down-regulating uPA expression.

Chemosensitivity of radioresistant cells in the multicellular spheroids of A549 lung adenocarcinoma.

BACKGROUND: The relapse of cancer after radiotherapy is a clinical knotty problem. Previous studies have demonstrated that the elevation of several factors is likely in some way to lead to the development of treatment tolerance, so it is necessary to further explore the problem of re-proliferated radioresistant cells to chemotherapeutic agents. In the present study, we aimed to investigate the chemosensitivity of radioresistant cells originated from the multicellular spheroids of A549 lung adenocarcinoma. METHODS: After irradiated with 25 Gy of 6 MV X-ray to A549 multicellular spheroids, whose 10th re-proliferated generations were employed as radioresistant cells, and the control groups were A549 parental cells and MCF7/VCR resistant cells. The chemo-sensitivity test was made by six kinds of chemotherapeutic drugs which were DDP, VDS, 5-Fu, HCP, MMC and ADM respectively, while verapamil (VPL) was used as the reversal agent. Then the treatment effect was evaluated by MTT assay, and the multidrug resistant gene expressions of mdr1 and MRP were measured by RT-PCR. RESULTS: Both A549 parental cells and A549 derived radioresistant cells were resistant to DDP, but sensitive to VDS, 5-Fu, HCP, MMC and ADM. The inhibitory rates of VPL to these two types of cell were 98% and 25% respectively (P < 0.001). In addition, without drugs added, the absorbance value (A value) of A549 parental cells was 2-folds higher than that of their radioresistant cells (P < 0.001). As to the MCF7/VCR cells, they were resistant to DDP and VDS, but slight sensitive to MMC, ADM, 5-Fu, and HCP with 80% of inhibitory rate to VPL. The subsequent RT-PCR demonstrated that the Mdr1/beta2-MG and MRP/beta2-MG of all A549 cells were about 0 and 0.7 respectively, and those of MCF7/VCR cells were 35 and 4.36. CONCLUSION: The chemosensitivity of A549 radioresistant cells had not changed markedly, and the decreased sensitivity to VPL could not be explained by the gene expression of mdr1 and MRP. It is possible that the changes in the cell membrane and decreased proliferate ability might be attributed to the resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to radioresistant cells. Therefore, the new biological strategy needs to be developed to treat recurring radioresistant tumor in combination with chemotherapy.

[Growth characteristics of A549 lung adenocarcinoma multicellular spheroid].

BACKGROUND: Owing to the limitation of monolayer tumour cells or transplanted tumor in radiation biology, multicellular spheroid (MTS) as a model of entity tumor had a wide range of application. This research aims to study the growth characteristics of A549 lung adenocarcinoma MTS so as to choose the best ones to perform experiments. METHODS: 1.75×107 A549 cells in 35mL were transfered into the 100mm incubator sealed with 2% agarose to have a rotating culture with 60r/min. After 40 hours every MTS was transfered into each of the 96 wells of multi-well plates coated with 2% agarose to have a static culture. RESULTS: During the rotation stage the MTS was round, the size was uniform, and the conjunction between cells was loose. After about 10 days of static culture, when the diameter of MTS at 429 to 570 µm the conjunction was close. After 26.5 days of static culture, the diameter of MTS became 1358.5 µm which could not be used for experiment. Observed under electron microscopy the cells in the MTS grew well without any apoptosis and necrosis. The cell cycle of MTS was dominated by G0 and G1 stage. CONCLUSIONS: Combination of rotating and static culture is a simple method to produce MTS which has similar growth characteristics with entity tumor and is best suitable for experiment research when the diameter is about 500 µm.

[Correlation of the uptake of technetium-99m methoxyisobutyl isonitrile with expression of multidrug resistance genes mdr-1 and MRP in human lung cancer].

OBJECTIVE: To investigate the relationship between the uptake of technetium-99m methoxyisobutyl isonitrile ((99m)Tc-MIBI) and the expression of multidrug resistance genes mdr-1 and MRP in lung cancer so as to guide chemotherapy. METHODS: Eighteen lung cancer patients were given 1 110 MBq(99m)Tc-MIBI intravenously. Chest single-photon emission-computed tomography was performed 60 and 120 min after the injection. The early and delay uptake rates and retain index of (99m)Tc-MIBI were calculated by the count ratio of the lung lesion to contralateral normal lung tissue. The expressions of mdr-1 and MRP genes in specimens of lung cancer and normal lung tissues near the cancers resected during operation among the 27 patients were detected with RT-PCR method. RESULTS: The positive rate of (99m)Tc-MIBI in the chest of lung cancer patients was 83.3% (15/18). The early uptake ratio of imaging in lung cancer patients was 1.99 +/- 0.64. After time decay correction, the rate of target to background and the retain index in 13 delay imagings were 2.06 +/- 0.69 and -45% approximately 33% respectively. In specimens of lung cancer, the positive expression rates of mdr-1 and MRP were 22.2%(6/27) and 63%(17/27) with the expression amount of 0.39 +/- 0.1 and 0.23 +/- 0.17 respectively. In specimens of normal lung tissues near lung cancer, the positive expression rates of mdr-1 and MRP genes were 35%(7/20) and 45.0%(9/20) with the expression amount of 0.44 +/- 0.14 and 0.17 +/- 0.18 respectively. In lung cancer tissues, the positive rate of MRP was higher than that of mdr-1 (P < 0.05), however, in the tissues near lung cancer, no significant difference was found between the positive rate of MRP and that of mdr-1 (P >< 0.05). There was no marked correlation (P >< 0.05) among the co-expression or expression of mdr-1 and/or MRP and the early uptake or retain index in lung cancer. CONCLUSION: The primary chemoresistance of lung cancer has not significant correlation to the expression of multidrug resistance genes mdr-1 and MRP. Other resistance mechanism may exist. (99m)Tc-MIBI imaging has not much clinical value in predicting the expression of mdr-1 and MRP genes.